Project Summary/Abstract The sixth Gordon Conference on Stem cells and Cancer will focus on how stem cell aging influences the initiation and progression of cancer. Aging leads to progressive impairments in stem cell functionality. There is increasing evidence that this leads to initiation and clonal selection of stem cells harboring genetic and epigenetic instability. The meeting will explore stem cell intrinsic factors that contribute to the initiation and selection of aberrant stem cell clones, but also the influence of stem cell extrinsic factors including alteration in the stem cell niche, the systemic blood circulatory environment, metabolism, and proliferative competition. There is tremendous interest in the aberrant reactivation of pathways that govern development and stem cell plasticity. Session on basic principles aim to improve our understanding of carcinogenesis across different organ systems including the hematopoietic system, skin, breast, intestine, brain, pancreas, and others. A therapeutic aim will be to target aging related mechanisms driving the clonal dominance of aberrant stem cells and tumor initiation as well as the plasticity and selection of sub-clones in cancers. There is also a GRS associated with the conference, allowing students and postdoctoral fellows to explore aging induced differences in signaling in cancer stem cells and normal stem cells and how organismal and tissue aging may influence this transition.